Abstract
Adenosine A2A receptors present in the central nervous system have been implicated in the modulation of motor functions. Accordingly, adenosine A2A receptor antagonists currently constitute an attractive non-dopaminergic option for use in the treatment of Parkinsons disease (PD). The highly enriched distributions of adenosine A2A receptors in striatopallidal neurons, and their ability to form functional heteromeric complexes with dopamine D2 and metabotropic glutamate mGlu5 receptors, render A2A receptor antagonists of particular interest in the modulation of motor behavior, whilst at the same time displaying a low predisposition to inducing non-motor side effects. Furthermore, adenosine A2A receptor antagonists appear to exert a marked efficacy on PD tremor and in reducing the progress of underlying neurodegeneration and maladaptive neuroplasticity that complicates standard dopamine replacement treatments in PD. Finally, recent evidence has illustrated an improvement of cognitive function as well as enhancement of attention in rodents following administration of A2A receptor antagonists. This article is aimed at examining preclinical studies describing these findings as well as reports from clinical trials, in order to provide a comprehensive review of the evidence suggesting that this class of drugs may represent an advance in the treatment of PD.
Keywords: Adenosine A2A receptor antagonist, Parkinson's disease, Basal Ganglia, clinical trials, neuroprotection, L-DOPA, dyskinesia, motor dysfunction
Current Pharmaceutical Design
Title: Adenosine A2A Receptor Antagonists and Parkinsons Disease: State of the Art and Future Directions
Volume: 14 Issue: 15
Author(s): N. Simola, M. Morelli and A. Pinna
Affiliation:
Keywords: Adenosine A2A receptor antagonist, Parkinson's disease, Basal Ganglia, clinical trials, neuroprotection, L-DOPA, dyskinesia, motor dysfunction
Abstract: Adenosine A2A receptors present in the central nervous system have been implicated in the modulation of motor functions. Accordingly, adenosine A2A receptor antagonists currently constitute an attractive non-dopaminergic option for use in the treatment of Parkinsons disease (PD). The highly enriched distributions of adenosine A2A receptors in striatopallidal neurons, and their ability to form functional heteromeric complexes with dopamine D2 and metabotropic glutamate mGlu5 receptors, render A2A receptor antagonists of particular interest in the modulation of motor behavior, whilst at the same time displaying a low predisposition to inducing non-motor side effects. Furthermore, adenosine A2A receptor antagonists appear to exert a marked efficacy on PD tremor and in reducing the progress of underlying neurodegeneration and maladaptive neuroplasticity that complicates standard dopamine replacement treatments in PD. Finally, recent evidence has illustrated an improvement of cognitive function as well as enhancement of attention in rodents following administration of A2A receptor antagonists. This article is aimed at examining preclinical studies describing these findings as well as reports from clinical trials, in order to provide a comprehensive review of the evidence suggesting that this class of drugs may represent an advance in the treatment of PD.
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Cite this article as:
Simola N., Morelli M. and Pinna A., Adenosine A2A Receptor Antagonists and Parkinsons Disease: State of the Art and Future Directions, Current Pharmaceutical Design 2008; 14 (15) . https://dx.doi.org/10.2174/138161208784480072
DOI https://dx.doi.org/10.2174/138161208784480072 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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